Polymorphism refers to the ability of a compound to assume at least two crystalline arrangements in the solid state. In the pharmaceutical industry, the polymorphic form of an active pharmaceutical ingredient (API) is relevant because it can affect the solubility and bioavailability of the drug. Consideration of polymorphism also helps reduce the risk of problems and costs during large scale production.
Fosnetupitant is a neurokynin-1 (“NK-1”) antagonist under development by Helsinn Healthcare SA, Lugano/Pazzallo Switzerland, for the treatment of chemotherapy induced nausea and vomiting. The compound is known chemically as 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium, and has the following chemical structure in its acidic/free base form:

The chloride monohydrochloride salt, and a method for its preparation, is described in WO 2013/082102. The chemical structure for this salt is reported as follows:

The molecule can be challenging to manufacture, particularly in a highly pure crystalline form in a commercially acceptable yield. Solvents used in the manufacture of the product pose special challenges. Prior art processes have removed these solvents via evaporative techniques, which can degrade the fosnetupitant due to the excessive heat.
Accordingly, it is an object of the present invention to provide novel crystalline forms of fosnetupitant, with improved purity, stability and ease of manufacture.
Another object of the present invention is to provide methods for making these crystalline forms.
Yet another object is to provide pharmaceutical dosage forms that make use of these novel crystalline forms, including methods of making such pharmaceutical dosage forms.
Still another object is to provide improved methods for isolating and purifying fosnetupitant without degrading the product.